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. 2021 Oct 8;2021(10):CD011611. doi: 10.1002/14651858.CD011611.pub3

Summary of findings 3. Memantine compared to placebo for adults with depression in bipolar disorder.

Mematine compared to placebo for adults with depression in bipolar disorder
Patient or population: adults (aged 18 years+) with depression in bipolar disorder
Setting: any setting (outpatient, inpatient, or both)
Intervention: memantine
Comparison: placebo
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Certainty of the evidence
(GRADE) Comments
Risk with placebo Risk with mematine
Efficacy: number of participants who respond to treatment ‐ at 1 week Study population OR 1.08
(0.06 to 19.05) 29
(1 RCT) ⊕⊝⊝⊝
VERY LOW1,2  
67 per 1000 72 per 1000
(4 to 576)
Efficacy: number of participants who respond to treatment ‐ at 2 weeks Study population OR 4.88
(0.78 to 30.29) 29
(1 RCT) ⊕⊝⊝⊝
VERY LOW1,2  
133 per 1000 429 per 1000
(107 to 823)
Efficacy: number of participants who respond to treatment ‐ at 4 weeks Study population OR 5.33
(1.02 to 27.76) 29
(1 RCT) ⊕⊝⊝⊝
VERY LOW1,2  
200 per 1000 571 per 1000
(203 to 874)
Efficacy: number of participants who respond to treatment ‐ at 3 months Study population OR 1.66
(0.69 to 4.03) 261
(2 RCTs) ⊕⊕⊝⊝
LOW1,3  
326 per 1000 445 per 1000
(250 to 661)
Efficacy: number of participants who achieve remission ‐ at 1 week Study population OR 1.08
(0.06 to 19.05) 29
(1 RCT) ⊕⊝⊝⊝
VERY LOW1,2  
67 per 1000 72 per 1000
(4 to 576)
Depression rating scale score ‐ at 3 months MD 0.6 lower (2.63 lower to 1.43 higher) 157
(1 RCT) ⊕⊕⊝⊝
LOW1  
Acceptability: total dropouts Study population OR 0.77
(0.45 to 1.31) 261
(2 RCTs) ⊕⊕⊝⊝
LOW1,3  
33 per 1000 278 per 1000
(184 to 396)
Moderate
275 per 1000 226 per 1000
(146 to 332)
Acceptability: dropouts due to adverse effects Study population OR 0.34
(0.01 to 8.34) 232
(1 RCT) ⊕⊕⊝⊝
LOW1,3  
9 per 1000 3 per 1000
(0 to 67)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; HDRS: Hamilton depression rating scale; OR: Odds ratio.
GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

1 Downgraded by one point because no studies described the outcome assessment as masked.
2 Downgraded by two points because of the very small sample size and the wide confidence interval.
3 Downgraded by one point because of wide confidence intervals.